Conventional endoscopes have a large field angle between 90° and 140° so that tissues inside the body can be observed without overlooking lesions, and they change the distance to the object in order to obtain enlarged or reduced images of an object to be observed. Thus, they are designed so as to have a large depth of field so that objects at a distance between 3 mm and 50 mm can be observed without focus adjustment, and they have an observation scale factor of approximately 30 to 50 when viewed on a 14 inch monitor screen, which is sufficient to observe diseased tissues.
In order to obtain additional magnification, zoom optical systems have been used with conventional endoscopes. The largest observation scale factor obtained with zoom optical systems is approximately 70 when viewed on a 14 inch monitor screen. The zoom optical system has a built-in zoom lens driving mechanism, and as a result, the endoscope has an insert tip with an outer diameter greater than 10 mm and requires complex operations. Such an endoscope has limited applications.
When an abnormality is difficult to diagnose by observation of tissue images, such as when a lesion is very small, suspicious tissues are generally excised using a therapeutic instrument in the course of an endoscopic observation. The excised tissues are then examined under a microscope.
An endoscope uses incident light illumination from an illumination optical system that is positioned around the objective optical system. A microscope uses an objective optical system and an illumination optical system that usually are positioned on opposite sides of the sample, with the sample usually being illuminated from the back (i.e., transmission light illumination is usually used). The sample will have been previously appropriately processed for observation. For example, it will have been thinly sliced so that it transmits light well. Often, the sample also will have been stained so as to provide images having improved contrast.
Laser-scanning-type, confocal endoscopes have been proposed that can be inserted into a living body and which have resolutions sufficient for cellular observation. There exist confocal optical systems which have a pinhole that passes light in an Airy disc light pattern, with the pinhole being positioned at a conjugate position to the image plane. Such optical systems acquire information of a diffraction-limited level for each point of an object surface in a field of view. A laser beam from an illumination optical system scans the object, and information obtained from light reflected by each point of the object surface is combined so as to produce an image representing either two-dimensional or three-dimensional information. Where three-dimensional information is obtained, high resolution is realized not only within a planar surface but also in the depth direction.
Conventional endoscopes require a wide field of view and have an image pickup unit that includes an image pickup element and an objective optical system having an image scale factor smaller than unity. Thus, object images are formed onto the image pickup surface of the image pickup unit in reduced size. Further, in order to assure an appropriate depth of field for observation, conventional endoscopes require a positional adjustment during assembly of the image pickup unit in which the image pickup surface of the image pickup element is fixed near the image plane of the objective optical system.
FIG. 1 shows the range of focus on the object side and on the image side for a conventional endoscope. In a conventional endoscope, the objective optical system projects the relative positional change between the object and the object-side leading surface of the objective optical system onto the image side at a reduced size. Therefore, it is somewhat difficult to find the best in-focus position since a small deviation from the best in-focus position corresponds to a large difference in object position that causes a de-focused state. In order to avoid this difficulty, the adjustment method illustrated in FIG. 1 is conventionally used. FIG. 1 shows the upper and lower limits ZoA and ZoB, respectively, in object space of an optical system having a desired depth of field (for example, at distances of 3 mm and 50 mm from the object-side leading surface of the objective optical system). The two corresponding images ZmA, ZmB are then formed as illustrated in reduced size and spacing. The mean position between the image-space positions ZmA and ZmB is determined, and the image pickup surface of the image pickup element is moved along the optical axis of the objective optical system in order to coincide with this mean position so as to achieve the optimum in-focus adjustment.
For a conventional endoscope, the image of an object will be formed by the objective optical system onto the image pickup surface of the image pickup element in reduced size even when the object is inclined relative to the objective optical system. Therefore, even when the object is inclined relative to the objective optical system, images on the image pickup surface will not be significantly asymmetric near the periphery of the field of view, and the captured image will not be subject to excessively unbalanced image aberrations. Thus, for focus adjustment of the image pickup unit of a conventional endoscope, excellent images can be obtained simply by ensuring mechanical accuracy of the focus adjustment apparatus.
On the other hand, a microscope has an objective optical system with an image scale factor having an absolute value greater than unity so as to form an image of an object that is enlarged in size. This also results in the depth of field on the object side being projected into image space with magnification. Therefore when focusing, a microscope commonly moves the stage on which the object is fixed rather than changing the position at which the image is observed.
As mentioned above, an objective optical system having an image scale factor with an absolute value greater than unity projects the relative positional change between the object and the object-side leading surface of the objective optical system onto the image side with magnification. Therefore, even when the image pickup surface of the image pickup element is positioned at the image plane of the objective optical system, the image on the image pickup surface will be significantly asymmetric near the periphery of the field of view when an object has its surface normal substantially inclined to the optical axis of the objective optical system. Such inclination causes the object surface to occupy significant depth in object space and causes adverse effects on the picked-up image with regard to balance of the aberrations. Thus, a sample for observation must be properly oriented on the microscope stage and the microscope stage on which the sample is fixed must be precisely adjusted relative to the objective optical system.
For the conventional way in which living tissues are removed and examined ex vivo, it takes from several days to several weeks to identity abnormal tissues. In addition, the cell sample that is isolated and fixed to be observed is only a tiny part of a removed tissue. Thus, although conventional ex vivo observation provides information on cellular structures, no functional information such as the fluid circulation within cells is provided because the circumstances are completely different from those of in vivo examination.
A small-sized image pickup unit with an objective optical system having a large scale factor comparable to that of a microscope and which has a high resolution is necessary in order to form clear cellular images of a lesion within a living body. The objective optical system used in conventional endoscopes does not meet such requirements. The objective optical system used in microscopes is satisfactory in performance, but is too large in diameter for insertion into a living body. Heretofore, no image pickup unit has been proposed that meets the above-discussed requirements. Laser-scanning-type, confocal endoscopes have a problem in that, at their present state of development, their scanning speed is too slow for providing in vivo, real-time observations. In addition, within a living body, an object cannot be fixed in a position where the objective optical system is accurately focused, as is possible when observing an excised sample using a microscope. Therefore, with the image pickup units, the image pickup surface of the image pickup element should be pre-adjusted to a fixed position that is suitable for in vivo cellular observation.
When image pickup units as discussed above are focused in the same manner as with a conventional endoscope, the following problems arise.
1) The objective optical system will have a significantly smaller depth of field and the relative positional change between the object and the object-side surface of the objective optical system will be projected onto the image side so as to be magnified in size. Thus, in order to adjust the position of the image pickup surface accurately, it is necessary to place the object used for focus adjustment with a precision and accuracy smaller than a micron (i.e., in sub-microns). This makes the focus adjustment difficult to reproduce consistently.
2) Although positioned within the mechanical accuracy of the focus adjustment apparatus, if an object surface is oriented so that its surface normal is significantly inclined to the optical axis of the objective optical system, the image on the image pickup surface of the image pickup element will be asymmetric near the periphery of the field of view, causing noticeable adverse effects on the captured images (i.e., the asymmetry itself causes the adverse effects).
3) An endoscope that is designed for use with its object-side surface of the objective optical system in contact with the object for observation has the near point of the depth of field at the objective optical system. Therefore, no object for focus adjustment can be placed at the near point of the depth of field.
Thus, a new focus adjustment method and a new focus range checking method are needed for magnifying endoscopes that allow in vivo, real-time, magnified observation of intact living cells.